Sex hormones differentially contribute to Parkinson disease in males: A multimodal biomarker study

background and purpose: parkinson disease (PD) presents relevant sex-related differences in epidemiology, pathophysiology, and clinical features, with males being more vulnerable to the disease. sex hormones might have a role, as the experimental models suggest; however, human-based evidence is scarce. here, we integrated multimodal biomarkers to investigate the relationships between circulating sex hormones and clinical-pathological features in male PD patients.Methods: a cohort of 63 male PD patients underwent comprehensive clinical evaluation of motor and nonmotor disturbances; measurement of estradiol, testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) blood levels; and cerebrospinal fluid (CSF) assay of total alpha-synuclein, amyloid-beta-42, amyloid-beta-40, total tau, and phosphorylated-181 tau levels. a subgroup of 47 PD patients underwent brain volumetry by 3-T magnetic resonance imaging for further correlations. a control group of 56 age-matched individuals was enrolled for comparative analyses. results: male PD patients had higher estradiol and testosterone levels than controls. estradiol had independent inverse associations with movement disorder society-unified Parkinson's Disease Rating Scale Part 3 score and disease duration; it was also lower in nonfluctuating patients. Testosterone had inverse independent correlations with CSF a-synuclein and right globus pallidus volume. FSH and LH had age-dependent correlations with cognitive impairment and CSF amyloid-beta-42/amyloid-beta-40 ratio. conclusions: the study suggested that sex hormones could differentially contribute to clinical-pathological features of PD in male patients. whereas estradiol might have a protective role in motor impairment, testosterone might be involved in male vulnerability to PD neuropathology. gonadotropins instead might mediate age-dependent phenomena of amyloidopathy and cognitive decline.